The long-term effects of in utero exposure to organochlorine compounds is of great potential importance. These compounds, which are detectable in nearly 100% of humans worldwide, have been linked to impaired neurodevelopment in children. In addition, p,p'-DDE, the primary metabolite of DDT, is a weak estrogen, and an androgen receptor blocker at concentrations observed in humans. One objective of this project is to determine whether maternal serum concentration of DDE, obtained during pregnancy, is a risk factor for cryptorchidism, hypospadias and polythelia in male offspring. These malformations were chosen because they are markers of deficient androgen activity in utero. Other objectives are to determine whether in utero exposure to DDE is subsequently associated with an altered age at menarche in adolescent females and an increased risk of obesity in adolescent males, and whether in utero exposure to PCBs is associated with suboptimal muscle tone, reflexes, IQ and hearing during childhood. Work to date has demonstrated that these compounds can be recovered from the study population at relevant concentrations, and that the correlation between concentrations of these compounds in first and third trimester serum is sufficiently high to employ third-trimester serum as a surrogate for first-trimester exposure. Work completed in FY 2002 found that elevated maternal serum DDE was associated with a history of fetal loss (odds ratio for 60 mg/l=1.3, p for trend <0.05). Since DDT is still used for malaria control in many developing countries, these findings have important implications for international health. It was also found that maternal third-trimester serum PCB levels were not associated with adverse neurodevelopment in children at 8 months of age, although substantial center heterogeneity was noted. Work completed in 2003 demonstrated that in contrast to animal toxicology study results, maternal PCB exposure was not associated with sensorineural hearing loss in the offspring, nor was PCB exposure associated with cognitive ability at age 7. Work is in progress in the study of maternal serum DDE and PCB concentration as risk factors for prolonged time to achieve pregnancy.